Male sexual dysfunction, impotence, can result from a number of distinct problems. These include loss of desire or libido, the inability to maintain an erection, premature ejaculation, lack of emission, and inability to achieve an orgasm. Frequently, more than one of these problems present themselves simultaneously. The conditions maybe secondary to other disease states (typically chronic conditions), the result of specific disorders of the urogenital system or endocrine system, secondary to treatment with pharmacological agents (e.g. antihypertensive drugs, antidepressant drugs, antipsychotic drugs, etc.) or the result of psychiatric problems.
The present invention deals with the inability to obtain or maintain an erection which is due to physiologic factors. The present invention does not deal with psychogenically caused erectile impotence. Galanthamine has been reported as useful in the treatment of psychogenic form of sexual asthenia in Savr. Med. (Bulgaria), 1974, 25/12 (30-34).
Physiologic erectile impotence differs from psychogenic erectile impotence in significant ways and one can readily separate the two types. From early childhood through at least the eighties, erections occur during normal sleep and is known as nocturnal penile tumescence or NPT. This happens during rapid eye movement (REM) sleep and the total NPT time per night averages about 100 min. These erections continue to occur in patients having the psychogenic form of erectile impotence while they do not occur in men with physiological causes for their impotence. Therefore, the simple observation that erectile function is present during sleep indicates that a psychogenic cause rather than a physiologic cause is at work. Alternative means for a differential diagnosis between the psychogenically and physiologically mediated condition include the use of a strain gauge with recorder or wrapping with perforated paper and noting failure to rupture the perforations.
According to Harrison's Principles of Internal Medicine, 10th Ed. pp. 240-243 (1983), medical therapy for impotence has included androgens (useful only in hypogonadal men), bromocriptine or surgical treatment (for prolactin secreting pituitary tumor), surgery for aortic obstruction, and implantation of prosthetic devices. As stated above, galanthamine, a cholinergic drug believed potentially to be useful for Senile Demetia of the Alzheimer's Type (SDAT), has been reported to alleviate the psychogenic form of erectile impotence.
As far as the present inventor is aware there is no suitable therapeutic substance available for the treatment of physiologic male erectile impotence. Recently, certain tetrahydrobenzindole serotonin agonists (such as those in EP-A 392,768) have been alleged to be of value in improving sexual function, particularly male potency. U.S. Pat. No. 4,530,920 mentions peptides useful in hypogonadal conditions and impotence; however, it appears that the activity of the peptide disclosed there is related to its androgen stimulation. As such, it would not be expected to be of any value in conditions where hypogonadism is not at issue.
Physostigmine has been used to obtain an ejaculation from paraplegic men (Andrologia 20 (4):311-3, July-August 1988). Neostigmine has been used intrathecally to obtain a sample from a paraplegic male for artificial insemination purposes (Paraplegia 24 (1):32-7, 1986 Feburary).
The United States Pharmacopoeia, 9.sup.th Edition lists papaverine and phentolamine as useful in impotence. Papaverine is an opium alkaloid and it relaxes smooth muscle in the ureter and blood vessels. Phentolamine is an adrenergic inhibitor, while physostigmine and neostigmine are cholinergic agents.